Many anti-cancer drugs have a mechanism of inhibiting the division of cancer cells, whose growth control breaks down. Since such anti-cancer drugs exhibit extremely effective anti-cancer functions, they are valuable in use; however, the anti-cancer drugs also exhibit a cell-growth inhibiting function on normal cells, which causes many side effects and thus often prevents its use.
For this reason, anti-cancer drugs have required DDS techniques that specifically deliver drugs to cancer cells without acting on normal cells. To reduce side effects, various anti-cancer drugs are combined with DDS techniques, and developed. One preferably used DDS technique is a technique using a liposome comprising a lipid bilayer membrane.
For example, a technique using a liposome and a platinum anti-cancer agent such as oxaliplatin, cisplatin, or carboplatin has been developed (PTL 1). To introduce such an anti-cancer drug using a remote loading method, only a weakly basic anti-cancer drug can be used. To solve this problem, a remote loading method utilizing a solubility gradient has been developed; however, this method only applies to highly water-soluble drugs, and the introduction efficiencies of these drugs are very low (PTL 2).
On the other hand, paclitaxel, docetaxel, etc., which have been applied to breast cancers, cervical cancers, etc., are practically insoluble in water; therefore, they are prepared at the time of use by dissolving them in a solvent such as alcohol, and then administered. This, however, requires time, and involves risk.
For the purpose of improving the solubility of paclitaxel, docetaxel, etc., in water, various paclitaxel derivatives have been produced. For example, as shown in NPL 1, a technique of adding a monosaccharide such as glucose, galactose, mannose, xylose, or the like, to paclitaxel has been developed.
Unfortunately, even such paclitaxel derivatives, e.g., paclitaxel monoglycosides and docetaxel monoglycosides do not have sufficient water solubility, and there has been no knowledge of a DDS formulation obtained by combining paclitaxel derivatives and a liposome.